Longer-Term OrigAMI-1 Results Highlight Durable Activity of Amivantamab-Based Regimens in Metastatic Colorectal Cancer
Johnson & Johnson has announced encouraging longer-term follow-up results from the Phase 1b/2 OrigAMI-1 clinical study evaluating amivantamab-vmjw, an investigational bispecific antibody targeting both epidermal growth factor receptor (EGFR) and MET. The study assessed amivantamab in combination with standard chemotherapy regimens FOLFOX or FOLFIRI in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC), a population with limited effective treatment options following disease progression.
The newly presented data demonstrate sustained anti-tumor activity, durable responses, and a favorable tolerability profile, reinforcing the rationale for continued development of amivantamab-based regimens in colorectal cancer. These findings were shared during a poster presentation at the 2026 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium (Abstract #166).
According to Dr. Filippo Pietrantonio, M.D., Head of the Gastrointestinal Oncology Unit at the IRCCS Foundation National Cancer Institute in Milan, the durability of responses observed in the study is particularly notable. He emphasized that some patients maintained clinical benefit for more than two years, including individuals with liver metastases—a subgroup historically associated with poorer outcomes. These prolonged responses suggest meaningful progress in a disease setting where long-term disease control has remained difficult to achieve.
Addressing Unmet Needs in Metastatic Colorectal Cancer
Colorectal cancer remains the third most commonly diagnosed cancer worldwide and is a leading cause of cancer-related mortality. While it has traditionally affected older adults, incidence rates among individuals under 50 continue to rise. More than half of patients will ultimately develop metastatic disease, and approximately 70 percent of these patients experience liver involvement during the course of their illness.
Despite advances in systemic therapy, resistance to standard first-line treatments often develops early in metastatic colorectal cancer, limiting long-term benefit. For patients with RAS/BRAF wild-type disease who experience progression, second-line treatment options are constrained, with historical response rates ranging from 32 to 36 percent and median progression-free survival of approximately five to six months when treated with EGFR inhibitors in combination with chemotherapy. Emerging evidence has identified MET pathway alterations as a key mechanism of resistance to EGFR-directed therapies, underscoring the need for dual-pathway targeting strategies.
Amivantamab is uniquely designed to target both EGFR and MET, offering a potential approach to overcoming resistance mechanisms that limit the effectiveness of existing therapies.
OrigAMI-1 Study Design and Patient Population
The Phase 1b/2 OrigAMI-1 study included multiple cohorts, with Cohorts D and E focusing on patients with RAS/BRAF wild-type metastatic colorectal cancer treated with intravenous amivantamab either as monotherapy or in combination with FOLFOX or FOLFIRI chemotherapy. Eligible patients were confirmed to be negative for KRAS, NRAS, BRAF, and EGFR mutations and did not have HER2 amplification. Participants could have received up to one prior line of systemic therapy in the metastatic setting, and prior exposure to EGFR inhibitors was not allowed.
The primary endpoint of the study was safety, while secondary endpoints included overall response rate (ORR), duration of response (DOR), clinical benefit rate, and progression-free survival (PFS). Overall survival was evaluated as an exploratory endpoint.
Efficacy Outcomes Demonstrate Early and Durable Responses
At a median follow-up of 16 months, patients receiving amivantamab in combination with either FOLFOX (n=20) or FOLFIRI (n=23) achieved a confirmed overall response rate of 51 percent across the study population. Responses were observed relatively early, with a median time to first response of just over eight weeks. Median duration of response was 9.3 months, highlighting the durability of clinical benefit.
Median progression-free survival for the overall population was 9.2 months, while median overall survival had not yet been reached at the time of data cutoff. Outcomes were particularly encouraging in the first-line treatment subgroup, where patients achieved an ORR of 73 percent and median duration of response had not yet been reached. Notably, four of the 11 patients treated in the first-line setting were able to proceed to surgery with curative intent.
In the second-line subgroup, which included 32 patients, the overall response rate was 44 percent, with a median duration of response of 7.4 months. More than one-third of these patients remained on therapy for over one year, and three individuals continued treatment for longer than two years, further underscoring the durability of benefit.
Among patients with liver metastases, a historically challenging population, the study demonstrated an ORR of 57 percent and a median progression-free survival of 11.3 months, suggesting meaningful activity in this high-risk subgroup.
Safety Profile Consistent With Prior Experience
The safety findings from OrigAMI-1 were consistent with previously reported data for amivantamab combined with chemotherapy and aligned with the known safety profiles of the individual agents. Treatment-emergent adverse events were primarily associated with EGFR and MET inhibition or chemotherapy-related effects. Only four patients discontinued treatment due to therapy-related adverse events, representing 9 percent of the study population. Neutropenia was the most common Grade 3 or higher adverse event, and no new safety signals were identified.
Ongoing Phase 3 Development
Kiran Patel, M.D., Vice President and Global Head of Solid Tumor Clinical Development and Companion Diagnostics at Johnson & Johnson Innovative Medicine, noted that treatment paradigms for metastatic colorectal cancer have remained largely unchanged for many years. He emphasized that the company is leveraging its experience with EGFR-driven lung cancers to explore the broader potential of amivantamab’s dual EGFR and MET targeting strategy across colorectal cancer and other solid tumors.
Building on the OrigAMI-1 findings, global Phase 3 studies OrigAMI-2 and OrigAMI-3 are currently underway. These randomized trials are evaluating subcutaneous amivantamab in combination with FOLFOX or FOLFIRI in both first- and second-line metastatic colorectal cancer, with the goal of further defining the role of amivantamab-based regimens in this setting.
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